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Elli, Stefano ; Bojkova, Denisa ; Bechtel, Marco ; Vial, Thomas ; Boltz, David ; Muzzio, Miguel ; Peng, Xinjian ; Sala, Federico ; Cosentino, Cesare ; Goy, Andrew ; Guerrini, Marco ; Müller, Lutz ; Cinatl, Jindrich ; Margitich, Victor ; Velthuis, Aartjan J. W. te
Pandemic SARS-CoV-2 causes a mild to severe respiratory disease called coronavirus disease 2019 (COVID-19). While control of the SARS-CoV-2 spread partly depends on vaccine-induced or naturally acquired protective herd immunity, antiviral strategies are still needed to manage COVID-19. Enisamium is an inhibitor of influenza A and B viruses in cell culture and clinically approved in countries of the Commonwealth of Independent States. In vitro, enisamium acts through metabolite VR17-04 and inhibits the activity of the influenza A virus RNA polymerase. Here we show that enisamium can inhibit coronavirus infections in NHBE and Caco-2 cells, and the activity of the SARS-CoV-2 RNA polymerase in vitro. Docking and molecular dynamics simulations provide insight into the mechanism of action and indicate that enisamium metabolite VR17-04 prevents GTP and UTP incorporation. Overall, these results suggest that enisamium is an inhibitor of SARS-CoV-2 RNA synthesis in vitro.
Kumpf, Oliver ; Giamarellos-Bourboulis, Evangelos ; Koch, Alexander ; Hamann, Lutz ; Mouktaroudi, Maria ; Oh, Djin-Ye ; Latz, Eicke ; Lorenz, Eva ; Schwartz, David A. ; Ferwerda, Bart ; Routsi, Christina ; Skalioti, Chryssanthi ; Kullberg, Bart-Jan ; Meer, J.W.M. van der ; Schlag, Peter M. ; Netea, Mihai G. ; Zacharowski, Kai ; Schumann, Ralf R.
Introduction: It has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies of single nucleotide polymorphisms (SNPs) within the endotoxin receptor and its signaling system showed an association with the risk of disease development. This study aims to examine the response associated with genetic variations of TLR4, the receptor for bacterial LPS, and a central intracellular signal transducer (TIRAP/Mal) on cytokine release and for susceptibility and course of severe hospital acquired infections in distinct patient populations. Methods: Three intensive care units in tertiary care university hospitals in Greece and Germany participated. 375 and 415 postoperative patients and 159 patients with ventilator associated pneumonia (VAP) were included. TLR4 and TIRAP/Mal polymorphisms in 375 general surgical patients were associated with risk of infection, clinical course and outcome. In two prospective studies, 415 patients following cardiac surgery and 159 patients with newly diagnosed VAP predominantly caused by Gram-negative bacteria were studied for cytokine levels in-vivo and after ex-vivo monocyte stimulation and clinical course. Results: Patients simultaneously carrying polymorphisms in TIRAP/Mal and TLR4 and patients homozygous for the TIRAP/Mal SNP had a significantly higher risk of severe infections after surgery (odds ratio (OR) 5.5; confidence interval (CI): 1.34 - 22.64; P = 0.02 and OR: 7.3; CI: 1.89 - 28.50; P < 0.01 respectively). Additionally we found significantly lower circulating cytokine levels in double-mutant individuals with ventilator associated pneumonia and reduced cytokine production in an ex-vivo monocyte stimulation assay, but this difference was not apparent in TIRAP/Mal-homozygous patients. In cardiac surgery patients without infection, the cytokine release profiles were not changed when comparing different genotypes. Conclusions: Carriers of mutations in sequential components of the TLR signaling system may have an increased risk for severe infections. Patients with this genotype showed a decrease in cytokine release when infected which was not apparent in patients with sterile inflammation following cardiac surgery.
On the current psychotherapeutic situation for persons with pornography use disorder in Germany
(2023)
Markert, Charlotte ; Storz, Florian ; Golder, Sarah ; Rechmann, Johanna ; Rubel, Julian ; Lalk, Christopher ; Vogt, Rabea ; Glombiewski, Julia Anna ; Braun, David ; Pané-Farré, Christiane A. ; Michael, Tanja ; Mattheus, Hannah K. ; Dominick, Nanne ; Wölfling, Klaus ; Lutz, Wolfgang ; Schaffrath, Jana ; Stangier, Ulrich ; Kananian, Schahryar ; Strüwing, Dirk ; Klingelhöfer, Doerthe ; Valbert, Frederik Tim ; Neumann, Anja ; Walter, Bertram ; Stark, Rudolf
Background and aims: For the first time, the ICD-11 provides the diagnosis compulsive sexual behavior disorder (CSBD) that can be assigned for pornography use disorder (PUD). This study aimed to estimate the prevalence of PUD and associated consequences in Germany, to identify the psychotherapy demand among likely PUD (lPUD) cases and the treatment supply in different psychotherapeutic settings, to survey psychotherapists' level of expertise regarding PUD, and to identify predictors for psychotherapy demand.
Methods: Four studies were conducted: 1. Online study in the general population (n = 2070; m = 48.9%, f = 50.8%, d = 0.2%), 2. Survey among practicing psychotherapists (n = 983), 3. Survey of psychotherapists in psychotherapeutic outpatient clinics (n = 185), 4. Interviews with psychotherapeutic inpatient clinics (n = 28).
Results: The estimated prevalence of lPUD in the online study was 4.7% and men were 6.3 times more often affected than women. Compared to individuals without PUD, individuals with lPUD more often indicated negative consequences in performance-related areas. Among lPUD cases, 51.2% of men and 64.3% of women were interested in a specialized PUD treatment. Psychotherapists reported 1.2%–2.9% of lPUD cases among their patients. 43.2%–61.5% of psychotherapists stated to be poorly informed about PUD. Only 7% of psychotherapeutic inpatient clinics provided specific treatments to patients with PUD. While, among other factors, negative consequences attributed to lPUD were predictive for psychotherapy demand, weekly pornography consumption, subjective well-being, and religious attachment were not.
Discussion and conclusions: Although PUD occurs quite often in Germany, availability of mental health care services for PUD is poor. Specific PUD treatments are urgently needed.
Schulte-Oehlmann, Ulrike ; Albanis, Triantafyllos ; Allera, Axel ; Bachmann, Jean ; Berntsson, Pia ; Beresford, Nicola ; Carnevali, Daniela Candia ; Ciceri, Francesca ; Dagnac, Thierry ; Falandysz, Jerzy ; Galassi, Silvana ; Hala, David ; Janer, Gemma ; Jeannot, Roger ; Jobling, Susan ; King, Isabella ; Klingmüller, Dietrich ; Kloas, Werner ; Kusk, Kresten Ole ; Levada, Ramon ; Lo, Susan ; Lutz, Ilka ; Oehlmann, Jörg ; Oredsson, Stina ; Porte, Cinta ; Rand-Weaver, Marian ; Sakkas, Vasilis ; Sugni, Michela ; Tyler, Charles ; Aerle, Ronny van ; Ballegoy, Christoph van ; Wollenberger, Leah
Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body’s signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult. A major concern is that some of these EDCs appear to be biologically active at extremely low concentrations. There is growing evidence to indicate that the guiding principle of traditional toxicology that “the dose makes the poison” may not always be the case because some EDCs do not induce the classical dose–response relationships. The European Union project COMPRENDO (Comparative Research on Endocrine Disrupters—Phylogenetic Approach and Common Principles focussing on Androgenic/Antiandrogenic Compounds) therefore aims to develop an understanding of potential health problems posed by androgenic and antiandrogenic compounds (AACs) to wildlife and humans by focusing on the commonalities and differences in responses to AACs across the animal kingdom (from invertebrates to vertebrates).
Hülsdünker, Thorben ; Friebe, David ; Giesche, Florian ; Vogt, Lutz ; Pfab, Florian ; Haser, Christian ; Banzer, Winfried
Background/Objectives: Agility and cognitive abilities are typically assessed separately by different motor and cognitive tests. While many agility tests lack a reactive decision-making component, cognitive assessments are still mainly based on computer-based or paper-pencil tests with low ecological validity. This study is the first to validate the novel SKILLCOURT technology as an integrated assessment tool for agility and cognitive-motor performance.
Methods: Thirty-two healthy adults performed agility (Star Run), reactive agility (Random Star Run) and cognitive-motor (executive function test, 1-back decision making) performance assessments on the SKILLCOURT. Cognitive-motor tests included lower limb responses in a standing position to increase the ecological validity when compared to computer-based tests. Test results were compared to established motor and agility tests (countermovement jump, 10 m linear sprint, T-agility tests) as well as computer-based cognitive assessments (choice-reaction, Go-NoGo, task switching, memory span). Correlation and multiple regression analyses quantified the relation between SKILLCOURT performance and motor and cognitive outcomes.
Results: Star Run and Random Star Run tests were best predicted by linear sprint (r = 0.68, p < 0.001) and T-agility performance (r = 0.77, p < 0.001), respectively. The executive function test performance was well explained by computer-based assessments on choice reaction speed and cognitive flexibility (r = 0.64, p < 0.001). The 1-back test on the SKILLCOURT revealed moderate but significant correlations with the computer-based assessments (r = 0.47, p = 0.007).
Conclusion: The results support the validity of the SKILLCOURT technology for agility and cognitive assessments in more ecologically valid cognitive-motor tasks. This technology provides a promising alternative to existing performance assessment tools.
Barth, Klaus ; Belov, Alexander ; Beltran, Berta ; Bräuninger, Heinrich ; Carmona, José Manuel ; Collar, Juan I. ; Dafni, Theopisti ; Davenport, Martyn ; Di Lella, Luigi ; Eleftheriadis, Christos ; Englhauser, Jakob ; Fanourakis, George ; Ferrer-Ribas, Ester ; Fischer, Horst ; Franz, Jürgen ; Friedrich, Peter ; Galán, Javier ; García, J. A. ; Geralis, Theodoros ; Giomataris, Ioanis ; Gninenko, Sergei ; Gómez, Héctor ; Hasinoff, Michael D. ; Heinsius, Fritz-Herbert ; Hoffmann, Dieter H. H. ; Irastorza, Igor Garcia ; Jacoby, Joachim ; Jakovčić, Kresimir ; Kang, Donghwa ; Königsmann, Kay ; Kotthaus, Rainer ; Kousouris, Konstantinos ; Krčmar, Milica ; Kuster, M. ; Lakić, Biljana ; Liolios, Anastasios ; Ljubičić, Ante ; Lutz, Gerhard ; Luzón, Gloria ; Miller, David W. ; Papaevangelou, Thomas ; Pivovaroff, Mike J. ; Raffelt, Georg ; Redondo, Javier ; Riege, Hans ; Rodríguez, A. ; Ruz, Jaime ; Savvidis, Ilias ; Semertzidis, Yannis ; Stewart, Laura ; Van Bibber, Karl A. ; Vieira, Joaquin D. ; Villar, José A. ; Vogel, Julia K. ; Walckiers, Louis ; Zioutas, Konstantin
In non-hadronic axion models, which have a tree-level axion-electron interaction, the Sun produces a strong axion flux by bremsstrahlung, Compton scattering, and axiorecombination, the "BCA processes." Based on a new calculation of this flux, including for the first time axio-recombination, we derive limits on the axion-electron Yukawa coupling gae and axion-photon interaction strength ga using the CAST phase-I data (vacuum phase). For ma <~ 10 meV/c2 we find ga gae < 8.1 × 10−23 GeV−1 at 95% CL. We stress that a next-generation axion helioscope such as the proposed IAXO could push this sensitivity into a range beyond stellar energy-loss limits and test the hypothesis that white-dwarf cooling is dominated by axion emission.
Rhim, Hye Chang ; Tenforde, Adam ; Mohr, Lisa ; Hollander, Karsten Peter ; Vogt, Lutz ; Groneberg, Jan David Alexander ; Wilke, Jan
Objectiv:e To explore the association of physical activity (PA) with musculoskeletal pain (MSK pain).
Design: Cross-sectional study
Setting: 14 countries (Argentina, Australia, Austria, Brazil, Chile, France, Germany, Italy, the Netherlands, Singapore, South Africa, Spain, Switzerland and the USA).
Participants: Individuals aged 18 or older.
Primary and secondary outcome measures: PA volumes were assessed with an adapted version of the Nordic Physical Activity Questionnaire-short. Prevalence of MSK pain was captured by means of a 20-item checklist of body locations. Based on the WHO recommendation on PA, participants were classified as non-compliers (0–150 min/week), compliers (150–300 min/week), double compliers (300–450 min/week), triple compliers (450–600 min/week), quadruple compliers (600–750 min/week), quintuple compliers (750–900 min/week) and top compliers (more than 900 min/week). Multivariate logistic regression was used to obtain adjusted ORs of the association between PA and MSK pain for each body location, correcting for age, sex, employment status and depression risk.
Results: A total of 13 741 participants completed the survey. Compared with non-compliers, compliers had smaller odds of MSK pain in one location (thoracic pain, OR 0.77, 95% CI 0.64 to 0.93). Double compliance was associated with reduced pain occurrence in six locations (elbow, OR 0.70, 95% CI 0.50 to 0.98; forearm, OR 0.63, 95% CI 0.40 to 0.99; wrist, OR 0.74, 95% CI 0.57 to 0.98; hand, OR 0.57, 95% CI 0.40 to 0.79; fingers, OR 0.72, 95% CI 0.52 to 0.99; abdomen, OR 0.61, 95% CI 0.41 to 0.91). Triple to top compliance was also linked with lower odds of MSK pain (five locations in triple compliance, three in quadruple compliance, two in quintuple compliance, three in top compliance), but, at the same time, presented increased odds of MSK pain in some of the other locations.
Conclusion: A dose of 300–450 min WHO-equivalent PA/week was associated with lower odds of MSK pain in six body locations. On the other hand, excessive doses of PA were associated with higher odds of pain in certain body locations.
Friebe, David ; Sieland, Johanna ; Both, Hendrik ; Giesche, Florian ; Haser, Christian ; Hülsdünker, Thorben ; Pfab, Florian ; Vogt, Lutz ; Banzer, Winfried
Agility, as the ability to react rapidly to unforeseen events, is an essential component of football performance. However, existing agility diagnostics often do not reflect the complex motor–cognitive interaction required on the field. Therefore, this study evaluates the criterion and ecological validity of a newly developed motor–cognitive dual-task agility approach in elite youth football players and compare it to a traditional reactive agility test. Twenty-one male youth elite football players (age:17.4 ±0 .6; BMI:23.2 ± 1.8) performed two agility tests (reactive agility, reactive agility with integrated multiple-object-tracking (Dual-Task Agility)) on the SKILLCOURT system. Performance was correlated to motor (sprint, jump), cognitive (executive functions, attention, reaction speed) and football specific tests (Loughborough soccer passing test (LSPT)) as well as indirect game metrics (coaches' rating, playing time). Reactive agility performance showed moderate correlations to attention and choice reaction times (r = 0.48−0.63), as well as to the LSPT (r = 0.51). The dual-task agility test revealed moderate relationships with attention and reaction speed (r = 0.47−0.58), executive functions (r = 0.45−0.63), as well as the game metrics (r = 0.51−0.61). Finally, the dual-task agility test significantly differentiated players based on their coaches' rating and playing time using a median split (p < 0.05; d = 0.8–1.28). Motor–cognitive agility performance in elite youth football players seems to be primarily determined by cognitive functions. The integration of multiple object tracking into reactive agility testing seems to be an ecologically valid approach for performance diagnostics in youth football.
Highlights
* The study introduces a novel motor–cognitive dual-task agility approach (incorporation of multiple-object-tracking in agility testing), evaluating its criterion and ecological validity in elite youth football players compared to a standard agility test.
* The standard agility test was shown to have moderate correlations with attention and choice reaction times, while the dual-task agility approach additionally incorporates executive functions
* While the agility test correlates to football-specific test performance, the dual-task agility test significantly discriminates players based on their potential ratings and in-season playing time, highlighting its potential as a valuable tool for assessing performance in youth football.
* The findings suggest that agility performance in elite youth football is primarily determined by cognitive functions
* Incorporating more complex cognitive elements such as multiple-object-tracking in agility testing may improve ecological validity and therefore the predictive value of the testing procedure.